B-cell chronic lymphocytic leukemia-derived dendritic cells stimulate allogeneic T-cell response and express chemokines involved in T-cell migration

Abstract

Despite discovery of new therapeutic agents, including nucleoside analogs and monoclonal antibodies, the B-cell chronic lymphocytic leukemia (B-CLL) remains incurable. In recent years, some effort has been made in developing T-cell specific immunity against neoplasmatic cells. Reconstitution of effective costimulation and immunological response of host T-cells against CLL cells could be a potential approach in immunotherapeutic trials. CD40/CD40L system is involved in the survival and proliferation of normal and neoplasmatic B-cells. Some preclinical studies have shown that CD40 stimulation can differentiate leukemic cells into dendritic cells (DCs) and result in host response. In this study, we sought to determine whether B-CLL cells could be turned into efficient and functional antigen presenting cells, as well as to assess the type of allogeneic T-cell response against B-CLL - derived DCs.

Material and methods: B-CLL cells from 25 patients were cultured with or without the presence of CD40L and IL-4 for 96 hours and then cultured in mixed lymphocyte reaction with allogeneic T-cells.

Results: 1) after CD40 stimulation B-CLL cells achieved phenotypical and functional characterization of DCs (i.e. upregulated co-stimulatory and adhesion molecules at mRNA and protein level) 2) leukemia-derived DCs expressed higher amount of mRNA for chemokines involved in T-cell migration (MDC, TARC and CCR7) 3) the proliferating response of Tcells against leukemia-derived DCs consisted of CD4 and CD8 cells (upregulation of HLA-DR and OX40).

Conclusions: our experiment confirm that B-CLL cells can be turned into dendritic-like cells, additionally, these cells express chemokines involved in T-cell migration and stimulate allogeneic response.